Covid 2019

Covid 2019

https://reasonandscience.catsboard.com/t2930-covid-2019

4th August 2024: The following is a collection from various sources, attempting to track down the source of the Corona Virus. I do not defend any view or position, since I think it's unclear what the original source is, if it is a mutation that occurred naturally, or if it was a product made in the Wuhan lab. I also do not defend any of the conspiracy theories mentioned below. It is upon the readers to decide what they want to believe, and what they find convincing, or not.  

The first documentary movie on CCP virus, Tracking Down the Origin of the Wuhan Coronavirus
https://www.youtube.com/watch?v=3bXWGxhd7ic&fbclid=IwAR0TWIz9QaVGsB0n9riEP-Eg1iRHBaxqMUv3oiyIftvmlJMV7-lSXhj2C0A

The proximal origin of SARS-CoV-2 17 March 2020
https://www.nature.com/articles/s41591-020-0820-9?fbclid=IwAR2YAvNq29Q_TKbKzRuaF14cbGl7grDwKvNgg3siQ5wVxdbi8fuJ5ngGtJM

Claim: Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus. Although the evidence shows that SARS-CoV-2 is not a purposefully manipulated virus, it is currently impossible to prove or disprove the other theories of its origin described here.

Response: This claim is entirely unsubstantiated and without merit.

New Study Claims SARS-CoV-2 Coronavirus Originated Naturalistically
http://darwins-god.blogspot.com/2020/04/new-study-claims-sars-cov-2-coronavirus.html


How can it be explained otherwise, that they made a meeting in October 2019, simulating a pandemic with Corona Virus, which eventually became reality, 3 months later ?
http://www.centerforhealthsecurity.org/event201/

Gordon Brown calls for global government to tackle coronavirus
https://www.theguardian.com/politics/2020/mar/26/gordon-brown-calls-for-global-government-to-tackle-coronavirus

Gordon Brown has urged world leaders to create a temporary form of global government to tackle the twin medical and economic crises caused by the Covid-19 pandemic.

L– A world of tighter top-down government control and more authoritarian leadership, with limited innovation and growing citizen pushback http://www.nommeraadio.ee/meedia/pdf/RRS/Rockefeller%20Foundation.pdf?fbclid=IwAR2yMBuZ95QJKV5QZweija80wSZPBoe8igrHDeKFrgDHf4XBf2T7v9dDbBgOCK STEP

In several European newspapers, the frontline is that prominent politicians demand that a suprastatal global organization take care of the pandemic, claiming that sovereign states individually are unable to handle it. What does that tell us? Here another example from today in the German Der Spiegel:

https://www.spiegel.de/politik/deutschland/gerd-mueller-im-interview-corona-besiegen-wir-nur-gemeinsam-in-der-welt-oder-nicht-a-a84f1727-c2bd-4087-849b-2f06a6a4adcf

Federal Minister Müller sees the crisis as a global wake-up call for cooperation. He calls for a world crisis team to fight the pandemic.

https://id2020.org/

What is the infamous ID2020? It is an alliance of public-private partners, including UN agencies and civil society. It’s an electronic ID program that uses generalized vaccination as a platform for digital identity. The program harnesses existing birth registration and vaccination operations to provide newborns with a portable and persistent biometrically-linked digital identity. GAVI, the Global Alliance for Vaccines and Immunization, identifies itself on its website as a global health partnership of public and private sector organizations dedicated to “immunization for all”. GAVI is supported by WHO, and needless to say, its main partners and sponsors are the pharma-industry.
https://www.globalresearch.ca/defending-humanity-against-elite-coup/5708017

https://www.lifesitenews.com/news/one-world-government-needed-to-cope-with-covid-19-says-former-british-pm

Nigel Farage, the leader of the Brexit Party, and a founding member of the UK Independence Party (UKIP), took issue with the former Labour Prime Minister’s advocacy for a world government.

“Gordon Brown doesn’t get it,” he tweeted this morning. “Globalisation is the cause of our problems, not our saviour.”

But English Catholic writer Laurence England found Brown’s advocacy more disturbing than naive.

“Gordon Brown does get it,” he tweeted in response. “The One World Government is about sheer power over populaces, not about helping people. They want a world of slaves. He was a key Bilderberg attendee.”

The Bilderberg meetings have been used as a forum for world elite

SARS-Cov-2 was engineered.
No one who looks into the matter thoroughly and thinks for themselves with any reasonable amount of brainpower can possibly come up with any other reasonable conclusion. There are no other reasonable conclusions.

SARS-Cov-2 exactly matches over 70% of the genome of a chimeric virus that was engineered in the Wuhan BSL-4 lab in 2014 in a gain-of-function research experiment funded by the University of North Carolina and published in Nature in 2015. That engineered virus was a SARS virus backbone wrapped in the casing of a pangolith (“bat”) coronavirus. It was a partial success because it could infect human cells in a pitri dish. But it was also a partial failure, because it could not thrive in human cells grafted into mice. The virus that currently threatens the world, SARS-Cov-2, obviously came out of the same Wuhan, China research lab that engineered the 2014 chimeric virus, and is an obvious intentional improvement on that older design. One of the ways SARS-Cov-2 is an obviously engineered improvement over the 2014 chimeric research virus is that SARS-Cov-2 infects humans using spikes with the same genetic sequence that allows HIV and Ebola to bind to human cells.
This is not speculation. This has all been published in research journals.

I think there is no argument to deny the following evidence. The Corona Virus does not occur in nature but is a product of manipulation in the laboratory. The note at the beginning of the Nature magazine demonstrates how the journal is concerned that the truth is being exposed. The article also elucidates, why this pandemic has not occurred in the past. People have sold and eaten bats and wild animals in all ages. Why did such an outbreak occur now? The Following gives the answer.

Engineered bat virus stirs debate over risky research

12 November 2015

https://www.nature.com/news/engineered-bat-virus-stirs-debate-over-risky-research-1.18787?fbclid=IwAR1KPHbWmuf50QEwZ_zufaCo2xfsZ8JlxjCvKqLa6Wn7pjD3HivFLtP-RWA

An experiment that created a hybrid version of a bat coronavirus — one related to the virus that causes SARS (severe acute respiratory syndrome) — has triggered renewed debate over whether engineering lab variants of viruses with possible pandemic potential is worth the risks. The researchers created a chimaeric virus, made up of a surface protein of SHC014 and the backbone of a SARS virus that had been adapted to grow in mice and to mimic human disease. The chimaera infected human airway cells — proving that the surface protein of SHC014 has the necessary structure to bind to a key receptor on the cells and to infect them. It also caused disease in mice, but did not kill them. But other virologists question whether the information gleaned from the experiment justifies the potential risk. Although the extent of any risk is difficult to assess, Simon Wain-Hobson, a virologist at the Pasteur Institute in Paris, points out that the researchers have created a novel virus that “grows remarkably well” in human cells. “If the virus escaped, nobody could predict the trajectory,” he says.

Creation of a chimaera
The argument is essentially a rerun of the debate over whether to allow lab research that increases the virulence, ease of spread or host range of dangerous pathogens — what is known as ‘gain-of-function’ research. In October 2014, the US government imposed a moratorium on federal funding of such research on the viruses that cause SARS, influenza and MERS (Middle East respiratory syndrome, a deadly disease caused by a virus that sporadically jumps from camels to people).

Other experiments in the study show that the virus in wild bats would need to evolve to pose any threat to humans — a change that may never happen, although it cannot be ruled out. Baric and his team reconstructed the wild virus from its genome sequence and found that it grew poorly in human cell cultures and caused no significant disease in mice.

“The only impact of this work is the creation, in a lab, of a new, non-natural risk,” agrees Richard Ebright, a molecular biologist and biodefence expert at Rutgers University in Piscataway, New Jersey. Both Ebright and Wain-Hobson are long-standing critics of gain-of-function research.

In their paper, the study authors also concede that funders may think twice about allowing such experiments in the future. "Scientific review panels may deem similar studies building chimeric viruses based on circulating strains too risky to pursue," they write, adding that discussion is needed as to "whether these types of chimeric virus studies warrant further investigation versus the inherent risks involved”.

Useful research
But Baric and others say the research did have benefits. The study findings “move this virus from a candidate emerging pathogen to a clear and present danger”, says Peter Daszak, who co-authored the 2013 paper. Daszak is president of the EcoHealth Alliance, an international network of scientists, headquartered in New York City, that samples viruses from animals and people in emerging-diseases hotspots across the globe.

Studies testing hybrid viruses in human cell culture and animal models are limited in what they can say about the threat posed by a wild virus, Daszak agrees. But he argues that they can help indicate which pathogens should be prioritized for further research attention.

Without the experiments, says Baric, the SHC014 virus would still be seen as not a threat. Previously, scientists had believed, on the basis of molecular modelling and other studies, that it should not be able to infect human cells. The latest work shows that the virus has already overcome critical barriers, such as being able to latch onto human receptors and efficiently infect human airway cells, he says. “I don't think you can ignore that.” He plans to do further studies with the virus in non-human primates, which may yield data more relevant to humans.

Bio-Unsafety Level 3: Could the Next Lab Accident Result in a Pandemic?
So-called gain-of-function pathogen research will likely receive closer scrutiny after three U.S. biolab incidents
By Helen Branswell on July 14, 2014
https://www.scientificamerican.com/article/bio-unsafety-level-3-could-the-next-lab-accident-result-in-a-pandemic/?fbclid=IwAR3mlykzBG4C8APeQ4rXAqA1a9GYE9GjDmmN9A2Q4gUwperDRO744usQxOU

Gain-of-function work on influenza viruses is too dangerous to undertake. Such studies take flu viruses found in nature and, in essence, try to make them more dangerous. The aim is to see what it would take for viruses like H5N1, which currently rarely infect people, to gain the ability to easily transmit to and among us. Coughs and sneezes propel human flu viruses through populations, and scientists have found that by adding mutations and passing viruses from ferret to ferret enough times, they can push bird viruses to spread that way among the animals, which often stand in for people in flu research.

The end result is the formation of nasty pathogens with the potential to trigger disastrous flu pandemics if they were ever to escape the confines of the labs. After all, in its wild form H5N1 kills about 60 percent of the people it infects.



Here is the Nanki University paper explaining how they found the furin protease cleavage (same cleavage mechanism HIV and Ebola use).

Researchers in India found this same conclusion months ago but were mocked until their paper was retracted...now independently confirmed.

http://chinaxiv.org/abs/202002.00004

Abstract: In 2019, the 2019 novel Coronavirus (2019-nCoV) has caused the pneumonia outbreak in Wuhan (a city of China). In our previous study, the analytical results showed that both 2019-nCoV and SARS coronavirus belongs to Betacoronavirus subgroup B (BB coronavirus), but have large differences. The most important finding was that the alternative translation of Nankai CDS could produce more than 17 putative proteins, which may be responsible for the host adaption. The genotyping of 13 viruses using the 17 putative proteins revealed the high mutation rate and diversity of betacoronavirus. The present study for the first time reported a very important mutation in the Spike (S) proteins of BB coronavirus. By this mutation, 2019-nCoV acquired a cleavage site for furin enzyme, which is not present in the S proteins of all other BB coronavirus (e.g. SARS coronavirus) except the Mouse Hepatitis coronavirus (MHV). This mutation may increase the efficiency of virus infection into cells, making 2019-nCoV has significantly stronger transmissibility than SARS coronavirus. Because of this mutation, the packing mechanism of the 2019-nCoV may be changed to being more similar to those of MHV, HIV, Ebola virus (EBoV) and some avian influenza viruses, other than those of all other BB coronavirus (e.g. SARS coronavirus) except the Mouse Hepatitis coronavirus (MHV). In addition, we unexpectedly found that some avian influenza viruses acquired a cleavage site for furin enzyme by mutation as 2019-nCoV. Further studies of this mutation will help to reveal the stronger transmissibility of 2019-nCoV and lay foundations for vaccine development and drug design of, but not limited to 2019-nCoV.


Following science paper supports evidence to the contrary of the hypothesis that the Covid is a lab product, but we don't know, if the lab experiments did go on, and viruses, after 2015, continued to be manipulated. The paper claims that Covid is the result of naturally occurring evolution. If that is the case, why have we not seen more frequently other cases as our current one, spreading globally, and infecting and killing inumerous people?  

No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2
Another claim in Chinese social media points to a Nature Medicine paper published in 2015 [7], which reports the construction of a chimeric CoV with a bat CoV S gene (SHC014) in the backbone of a SARS CoV that has adapted to infect mice (MA15) and is capable of infecting human cells [8]. However, this claim lacks any scientific basis and must be discounted because of significant divergence in the genetic sequence of this construct with the new SARS-CoV-2 (>5,000 nucleotides).

Upon careful phylogenetic analyses by multiple international groups [5,14], the SARS-CoV-2 is undoubtedly distinct from SL-SHC014-MA15, with >6,000 nucleotide differences across the whole genome. Therefore, once again there is no credible evidence to support the claim that the SARS-CoV-2 is derived from the chimeric SLSHC014-MA15 virus.

There are also rumours that the SARS-CoV-2 was artificially, or intentionally, made by humans in the lab, and this is highlighted in one manuscript submitted to BioRxiv (a manuscript sharing site prior to
any peer review), claiming that SARS-CoV-2 has HIV sequence in it and was thus likely generated in the laboratory. In a rebuttal paper led by an HIV-1 virologist Dr. Feng Gao, they used careful bioinformatics analyses to demonstrate that the original claim of multiple HIV insertions into the SARS-CoV-2 is not HIV-1 specific but random [15]. Because of the many concerns raised by the international community, the authors who made the initial claim have already withdrawn this report.
https://www.tandfonline.com/doi/pdf/10.1080/22221751.2020.1733440?needAccess=true



Coronavirus was developed in a Wuhan lab as a BioWeapon
http://mailstar.net/coronavirus.html?fbclid=IwAR3ipRbnuLFYkVRCpEJCs8etK-Iaocap3UQ5We_2u3yt7ZKuoTK55Q4xPMs

The proximal origin of SARS-CoV-2

17 March 2020

https://www.nature.com/articles/s41591-020-0820-9?fbclid=IwAR2YAvNq29Q_TKbKzRuaF14cbGl7grDwKvNgg3siQ5wVxdbi8fuJ5ngGtJM

Claim: Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus. Although the evidence shows that SARS-CoV-2 is not a purposefully manipulated virus, it is currently impossible to prove or disprove the other theories of its origin described here.

Response: This claim is entirely unsubstantiated and without merit.

New Study Claims SARS-CoV-2 Coronavirus Originated Naturalistically
http://darwins-god.blogspot.com/2020/04/new-study-claims-sars-cov-2-coronavirus.html

In fact, the rationale and explanation for their rather important conclusion is remarkably terse. The paper uses two pieces of evidence to argue against the theory that the virus arose via laboratory manipulation. And their rationale amounts only to a few sparse sentences, which I quote here. First, we have:

While the analyses above suggest that SARS-CoV-2 may bind human ACE2 with high affinity, computational analyses predict that the interaction is not ideal and that the RBD [receptor-binding domain] sequence is different from those shown in SARS-CoV to be optimal for receptor binding.

The argument boils down to this: The receptor-binding domain (RBD) in the SARS-CoV-2 spike protein binds with high affinity to the human ACE2 receptor, and in other species with high ACE2 similarity (sic, the paper erroneously refers to such high similarity as “high homology”), but that computational analyses fail to predict this, and instead predict “that the interaction is not ideal.” Therefore, they reason that the laboratory manipulation hypothesis is less likely because under that hypothesis, the observed SARS-CoV-2 RBD sequence would not have been designed. Instead, a designer would have selected a sequence with stronger predicted binding.

As you can see, this reasoning is fraught with unjustified assumptions about how a designer would have acted. The second argument is equally weak:

The second notable feature of SARS-CoV-2 is a polybasic cleavage site (RRAR) at the junction of S1 and S2, the two subunits of the spike. … Polybasic cleavage sites have not been observed in related “lineage B” betacoronaviruses, although other human betacoronaviruses, including HKU1 (lineage A), have those sites and predicted O-linked glycans. … if genetic manipulation had been performed, one of the several reverse-genetic systems available for betacoronaviruses would probably have been used. However, the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone.

To summarize, the authors make ever escalating claims of certainty, from a rather modest beginning of two, interesting but frankly weak, observations. The paper oversteps its bounds and should not have passed peer review.

https://www.youtube.com/watch?feature=youtu.be&v=fWhbxJRTtcc&fbclid=IwAR32OF4LNZLdNHsOfhRvZaxqOvdWmUsMhjtf1gOidc643sDwUnli6M5YSu8&app=desktop

What is being done in Denmark today, might soon be the way that many other countries will go:

https://www.thelocal.dk/20200313/denmark-passes-far-reaching-emergency-coronavirus-law

Denmark's parliament on Thursday night unanimously passed an emergency coronavirus law which gives health authorities powers to force testing, treatment and quarantine with the backing of the police.

And the vaccine could probably not be so far away:

Israeli Research Center to Announce It Developed Coronavirus Vaccine, Sources Say

Scientists at the Biological Research Institute are making significant breakthroughs in understanding coronavirus, the sources say, but a long process of pre-clinical and clinical trials is to follow

https://www.haaretz.com/israel-news/.premium-coronavirus-vaccine-israel-biological-research-institute-develope-1.8665074

Obviously, they did not find the solution in a month and a half. They knew probably beforehand what would come, and have an advantage now.....

Soon, the worldwide police state will be full at play. The red carpet for the strong man, Maytreya, is being prepared and rolled out. Luci Fer's dream becoming reality.

NWO is full at play !!

The paper goes on to explain how scientist have not seen anything like this in previous strains. But, it was not just a single anomaly. It adds: “Before the emergence of the 2019-nCoV, this important feature was not observed in other coronaviruses.  Strikingly, the 2019-nCoV sequence contains 12 additional nucleotides upstream of the single cleavage site.”

The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114094/

http://hlaoo1980.blogspot.com/2020/03/wuhan-virus-genetically-engineered-to.html

Wuhan Virus: Genetically Engineered To Infect Humans

https://www.express.co.uk/news/weird/1253135/coronavirus-genetically-engineered-bioweapon-wuhan-lab-leak-covid19-spt

A study released by Chinese scientists last week found the origin of coronavirus could have come from the Wuhan Institute of Virology, a level four biosafety laboratory 12km from the epicentre of the outbreak. Now, a new investigation, titled “Coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade,” suggests it has been genetically engineered too.

Published on Science Direct this month, the paper reads: “In 2019, a new coronavirus (2019-nCoV) infecting humans has emerged in Wuhan, China. “Its genome has been sequenced and the genomic information promptly released. Despite a high similarity with the genome sequence of SARS-CoV, we identified a peculiar furin-like cleavage site of the 2019-nCoV, lacking in the other SARS-like CoVs. In this article, we discuss the possible functional consequences of this cleavage site in the viral cycle, pathogenicity and its potential implication in the development of antivirals.”

Furin is a "highly expressed" protein found in the lungs of humans that could have been used to activate a virus that previously could have only been passed between animals. The experts believe this “peculiar furin” is an anomaly and could be used to “successfully exploit” enzymes that innate immunity in humans.

The paper goes on to explain how scientist have not seen anything like this in previous strains. But, it was not just a single anomaly. It adds: “Before the emergence of the 2019-nCoV, this important feature was not observed in other coronaviruses. Strikingly, the 2019-nCoV sequence contains 12 additional nucleotides upstream of the single cleavage site.”

The paper suggests that this part of the DNA chain has been tampered with for “gain-of-function to the 2019-nCoV for efficient spreading in the human population compared to other coronaviruses". It adds: “This possibly illustrates a convergent evolution pathway between unrelated CoVs.” But, for now, it is just a theory as further testing is needed before the scientists have concrete proof.

The paper continues: “Obviously much more work is needed to demonstrate experimentally our assertion, but the inhibition of such processing enzymes may represent a potential antiviral strategy."

The Perfect Virus.
Two gene tweeks that made it a killer.

"A very similar virus was detected years ago, but we failed to develop a proper vaccine.

The Virus

Here's what makes this Coronavirus so deadly:
1. It attaches perfectly — 10 times (!) better than the SARS virus — to receptors ubiquitously found in our lungs.
2. It is triggered by an enzyme (furin) of which our bodies produce copious amounts.

****

"Then it had the unbelievable misfortune to emerge in exactly the wrong place at exactly the wrong time.

“It’s got this beautifully adapted set of mutations,” says Holmes. In his published work, he calls it a “perfect epidemiological storm”.

The virus pulled from bats in 2013 could not infect humans. SARS-CoV-2 can. Why?

It appears that two tiny tweaks to the virus’ genetic code have made a huge difference.

CoV-2 wants to do two things: bind to a human cell and then get inside it. The virus binds to a cellular receptor – think of them as little antennae that stick off the side of human cells – called ACE2.

ACE2 receptors are designed to listen for signals that change our blood pressure. Fine adjustments to blood pressure are really important in our lungs, so our lung cells are covered in ACE2 receptors.

SARS was able to bind to ACE2. But small genetic changes mean CoV-2 binds almost perfectly, at least 10 times more tightly than SARS. “It’s beautifully adapted to do that,” says Holmes.

But that’s not enough. Once CoV-2 is stuck on a cell, it needs to get in. That’s where the second tweak comes in.

CoV-2 is covered in spikes. They act like tiny harpoons. The virus needs to stick to the cell and then fire a harpoon. The harpoon pulls the surface of the cell and the virus together, allowing them to fuse. That’s how the virus gets inside.

“But you don’t want the harpoon firing off randomly,” says Professor Stephen Turner, head of microbiology at Monash University. “You only want it to fire when it’s ready to infect the cell. If it’s going off too early or too late, the virus would not be able to infect us.”

To trigger the harpoon at just the right time, viruses rely on human enzymes, little proteins in our blood. Some enzymes trigger the harpoon too early, others trigger it too late. Among the best enzyme triggers – the one that fires the harpoon at exactly the right time – is an enzyme called furin. Our bodies produce heaps of furin.

“Basically, you can work out if a virus is going to be highly pathogenic or not if it is activated by furin,” says Turner.

Bird flu is triggered by furin. We got lucky, though, because it wasn’t very good at sticking to our cells. CoV-2 is great at sticking to our cells. And it’s triggered by furin, among the best triggers a virus can have.

“The combination is what makes it so infectious,” says Turner.””

[b]On the origin and continuing evolution of SARS-CoV-2[b]

https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa036/5775463?fbclid=IwAR174GpDnznMoqP-xNXQV-RUZQQTm9ReE7yDKLyoRoqbYqWks7Dl3UthuVE

Based on the information below, there is no certainty how much time it would take to get the mutation, which is bringing so much trouble to all of us. It could take 40 years, or 400 years, starting from a common ancestor with Bats. So it remains basically an open question about what is more credible, a product of the lab, or NS. I remain with the view, evaluating all information taken into consideration, that there are good reasons to believe that the Virus came from a Lab.


To date, the closest described relative to the nCoV-2019 novel coronavirus in a non-human host is a bat SARSr-CoV called RaTG13 (genbank accession MN996532 49, Zhou et al (2020) [1]) sampled from a Rhinolophus affinis bat in Yunnan Province in 2013.

With the faster rate this analysis suggests the human nCoV-2019 and the bat SARSr-CoV last shared a common ancestor around the end of 1992 and likely before mid-1997 (the upper 95% credible interval). For the slower rate this estimate is proportionally older — likely before 1978.

http://virological.org/t/divergence-of-ncov-2019-to-closest-non-human-relative/388

These viruses are known to recombine, but I don’t think we have a good idea yet what type of timescale is involved. Do they recombine on average once every 40 years, or once every 400 years?

The spike protein from the Wuhan strain is closer to RaTG13 overall, probably due to the S1-NTD subdomain being so different in the pangolin coronavirus. From the S1-CTD section on, the Wuhan strain and the pangolin strain are pretty similar (~97%), except for the furin cleavage site insertion.

It seems unlikely that the receptor binding domain–and especially the receptor binding motif–would be nearly identical to one found in pangolin through random chance.

The title of this post ideally needs updated as Matthew Wong’s reconstructed virus from the dead pangolin metagenomic data from

Liu et al 2019 https://www.mdpi.com/1999-4915/11/11/979/htm 99

is relatively close to the 2019-nCoV lineage throughout its genome, not just in Spike. It’s not, however, closer than the RaTG13 genome from bats.

The important question would seem to be whether the RBD similarity to SARS-CoV-2 is due to recombination or convergent evolution.

http://virological.org/t/ncov-2019-spike-protein-receptor-binding-domain-shares-high-amino-acid-identity-with-a-coronavirus-recovered-from-a-pangolin-viral-metagenomic-dataset/362

The emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and of the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 demonstrated that these zoonotic viruses can transmit to humans from various animal species, and suggested that additional emergence events are likely to occur. 7

Coronaviruses use S homotrimers to promote cell attachment and fusion of the viral and host membranes. S determines host range, cell tropism and is the main target of neutralizing antibodies during infection1. S is a class I viral fusion protein synthesized as a single chain precursor of about 1,300 amino acids that trimerizes upon folding. It is composed of an amino-terminal S1 subunit, containing the receptor-binding domain, and a carboxy-terminal S2 subunit, driving membrane fusion.

Cleavage by furin-like host proteases at the junction between S1 and S2 (S2 cleavage site) occurs during biogenesis for some coronaviruses. After virion uptake by target cells, a second cleavage is mediated by endo-lysosomal proteases (S2′ cleavage site), allowing fusion activation of coronavirus S proteins.

S can be activated by furin, a broadly expressed protease, by a two-step cleavage mechanism, occurring at distinct sites, with cleavage events temporally separated. Such furin-mediated activation is unusual in that it occurs in part during virus entry. 8

The coronavirus spike (S) glycoprotein initiates infection by promoting fusion of the viral and cellular membranes through conformational changes. 3 Coronaviruses are large enveloped viruses associated with up to 30% of respiratory tract infections in humans. Coronaviruses have also emerged as a global pandemic threat due the outbreaks of severe acute respiratory syndrome (SARS) and of Middle-East respiratory syndrome (MERS). SARS coronavirus (SARS-CoV) and MERS coronavirus (MERS-CoV) are the causative agents of these deadly pneumonias that demonstrated that coronaviruses could cross the species barrier from bats, camels, raccoons, or palm civets to humans

Coronavirus entry is mediated by the trimeric transmembrane spike (S) glycoprotein, which is responsible for receptor binding and fusion of the viral and host membranes. S is a class I viral fusion protein that is synthesized as a single-chain precursor of ∼1,300 amino acids and trimerizes upon folding. It forms an extensive crown decorating the virus surface. Coronavirus S proteins are comprised of two functional subunits, termed “S1” and “S2”.

The 180-kDa oligomeric S protein of the murine coronavirus mouse hepatitis virus strain A59 is posttranslationally cleaved into an S1 receptor binding unit and an S2 membrane fusion unit. 6  The spike (S) protein is the sole viral membrane protein responsible for cell entry. It binds to the receptor on the target cell and mediates subsequent virus-cell fusion

Protein S is cleaved at the S1–S2 junction during biosynthesis to separate the two major domains of the protein. The S1 domain is involved in receptor binding, and the S2 domain mediates the fusion step of the cell entry mechanism. During cell entry, the cleavage at S1–S2 primes S for the second cleavage at the S2′ site 11


Proposed model of coronavirus entry. 3
(A) The S glycoprotein promotes virus attachment to a host cell via binding to a transmembrane receptor using either domain A (e.g., MHV S) or domain B (e.g., SARS-CoV or MERS-CoV S). The prefusion MHV S trimer is shown with the S1 subunit depicted in gray and the S2 subunits colored by protomer.
(B) Upon receptor binding, activation of the S trimer occurs via protease cleavage at the S2′ site.
(C) Shedding of the S1 subunit trimer frees the fusion machinery, as reported for MERS-CoV (10).
(D) Subsequent conformational changes of the S glycoprotein result in fusion of the viral and host membranes. The postfusion MHV S2 trimer is depicted with each protomer in a different color. The transmembrane helices and the fusion peptides (FP) are connected to the MHV S trimer with dotted and solid lines, respectively.


Structure of 2019-nCoV S in the prefusion conformation. 2
(A) Schematic of 2019-nCoV S primary structure, colored by domain. Domains that were excluded from the ectodomain expression construct or could not be visualized in the final map are colored white. SS= signal sequence, 
NTD= N-terminal domain, 
RBD= receptor-binding domain, 
SD1= subdomain 1, 
SD2= subdomain 2, 
S1/S2= S1/S2 protease cleavage site, 
S2′= S2′ protease cleavage site, 
FP= fusion peptide, 
HR1= heptad repeat 1, 
CH= central helix, 
CD= connector domain, 
HR2= heptad repeat 2, 
TM= transmembrane domain, 
CT= cytoplasmic tail. 
Arrows denote protease cleavage sites. 

(B) Select 2D class averages of the particles that were used to calculate the 2019-nCoV S reconstruction (left). Side and top views of the prefusion structure of the 2019-nCoV S protein with a single RBD in the “up” conformation (right). The two RBD “down” protomers are shown as cryo-EM density in either white or gray and the RBD “up” protomer is shown in ribbons, colored corresponding to the schematic in Fig 1A.





Furin cleavage site in the SARS-CoV-2 coronavirus glycoprotein
The spike glycoprotein of the newly emerged SARS-CoV-2 contains a potential cleavage site for furin proteases. This observation has implications for the zoonotic origin of the virus and its epidemic spread in China. 1

The membrane of coronaviruses harbors a trimeric transmembrane spike (S) glycoprotein (pictured) which is essential for entry of virus particles into the cell. The S protein contains two functional domains: a receptor-binding domain, and a second domain which contains sequences that mediate fusion of the viral and cell membranes. The S glycoprotein must be cleaved by cell proteases to enable exposure of the fusion sequences and hence is needed for cell entry.

Proteolytic cleavage of the S glycoprotein can determine whether the virus can cross-species, e.g. from bats to humans.

Examination of the protein sequence of the S glycoprotein of SARS-CoV-2 reveals the presence of a furin cleavage sequence (PRRARS|V). The CoV with the highest nucleotide sequence homology, isolated from a bat in Yunnan in 2013 (RaTG-13), does not have the furin cleavage sequence. Because furin proteases are abundant in the respiratory tract, it is possible that SARS-CoV-2 S glycoprotein is cleaved upon exit from epithelial cells and consequently can efficiently infect other cells. The insertion of a furin cleavage site allowed a bat CoV to gain the ability to infect humans.

The question is: Was the furin cleavage acquired by recombination with another virus possessing that site?  

There are two necessary cleavages that must occur for infection. First, the S protein must be split into S1/S2, because those two sub-units mediate the distinct tasks of attachment and entry, respectively. Then the S2 must be cleaved at the “S2-prime” site, splitting the fusion peptide (FP) from the “internal fusion peptide” (IFP), because “it is likely both… participate in the viral entry process.” About the S2 cleaving, they say: “The furin-like S2′ cleavage site … is identical between the 2019-nCoV and SARS-CoV”.

2019-nCoV makes use of a densely glycosylated, homotrimeric class I fusion spike (S) protein to gain entry into host cells. 2

The S protein exists in a metastable prefusion conformation that undergoes a dramatic structural rearrangement to fuse the viral membrane with the host cell membrane. This process is triggered by binding of the S1 subunit to a host-cell receptor, which destabilizes the prefusion trimer, resulting in shedding of the S1 subunit and transition of the S2 subunit to a highly stable postfusion conformation.


The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clad 4
Strikingly, the 2019-nCoV S-protein sequence contains 12 additional nucleotides upstream of the single Arg↓ cleavage site 1 (Fig. 1, Fig. 2) leading to a predictively solvent-exposed PRRAR↓SV sequence, which corresponds to a canonical furin-like cleavage site (Braun and Sauter, 2019; Izaguirre, 2019; Seidah and Prat, 2012). This furin-like cleavage site, is supposed to be cleaved during virus egress (Mille and Whittaker, 2014) for S-protein “priming” and may provide a gain-of-function to the 2019-nCoV for efficient spreading in the human population compared to other lineage b betacoronaviruses.


Characterization of an nCoV-peculiar sequence at the S1/S2 cleavage site in the S-protein sequence, compared SARS-like CoV. 
Alignment of the coding and amino acid sequences of the S-protein from CoV-ZXC21 and 2019-nCoV at the S1/S2 site. The 2019-nCoV-specific sequence is in bold. The sequence of CoV-ZXC21 S-protein at this position is representative of the sequence of the other betacoronaviruses belonging to lineage b, except the one of 2019-nCoV.

What is the probability of insertion of four codons, twelve nucleotides, by natural selection? 



Surface glycoprotein (S) 13
(L=1273)

The Proteolytic Regulation of Virus Cell Entry by Furin and Other Proprotein Convertases 9
A wide variety of viruses exploit furin and other proprotein convertases (PCs) of the constitutive protein secretion pathway in order to regulate their cell entry mechanism and infectivity.

Proprotein convertases are a family of proteins that activate other proteins. Many proteins are inactive when they are first synthesized, because they contain chains of amino acids that block their activity. Proprotein convertases remove those chains and activate the protein. The prototypical proprotein convertase is furin 10

We generated a consensus sequence of 29,811 bp 5

What have we learned about the epidemic? 6
Based on current data, it seems as though SARS-CoV-2 mutates much more slowly than the seasonal flu. Specifically, SARS-CoV-2 seems to have a mutation rate of less than 25 mutations per year, whereas the seasonal flu has a mutation rate of almost 50 mutations per year.

Given that the SARS-CoV-2 genome is almost twice as large as the seasonal flu genome, it seems as though the seasonal flu mutates roughly four times as fast as SARS-CoV-2. 7



1. https://www.virology.ws/2020/02/13/furin-cleavage-site-in-the-sars-cov-2-coronavirus-glycoprotein/
2. https://www.biorxiv.org/content/10.1101/2020.02.11.944462v1.full.pdf
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651768/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114094/
5. https://mra.asm.org/content/9/11/e00169-20
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC167208/
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018210/
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210292/
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784293/
10. https://en.wikipedia.org/wiki/Proprotein_convertase
11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784293/
12. https://www.biorxiv.org/content/10.1101/2020.01.30.927871v1.full.pdf
13. https://zhanglab.ccmb.med.umich.edu/C-I-TASSER/2019-nCov/

Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018210/#CR6

Protein structure and sequence re-analysis of 2019-nCoV genome does not indicate snakes as its intermediate host or the unique similarity between its spike protein insertions and HIV-1
https://arxiv.org/ftp/arxiv/papers/2002/2002.03173.pdf

Bad News Wrapped in Protein: Inside the Coronavirus Genome
https://www.nytimes.com/interactive/2020/04/03/science/coronavirus-genome-bad-news-wrapped-in-protein.html?fbclid=IwAR26GgrthgirGMNmxZbDNg49NXHQES7hp-IHZM8J2hZsWyWXoC4jHqgwSoo

Moderate mutation rate in the SARS coronavirus genome and its implications
The non-synonymous and synonymous substitution rates were estimated to be 1.16 - 3.30 x 10-3 and 1.67 - 4.67 x 10-3 per site per year, respectively.

https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC446188&blobtype=pdf

Covid-19 had us all fooled, but now we might have finally found its secret.

Apr 5

ARDS: Acute Respiratory Distress Syndrome
DUR: drug utilization review
PEEP: Positive End Expiratory Pressure
SpO2: peripheral capillary oxygen saturation, an estimate of the amount of oxygen in the blood.

In the last 3–5 days, a mountain of anecdotal evidence has come out of NYC, Italy, Spain, etc. about COVID-19 and characteristics of patients who get seriously ill. It’s not only piling up but now leading to a general field-level consensus backed up by a few previously little-known studies that we’ve had it all wrong the whole time. Well, a few had some things eerily correct (cough Trump cough), especially with Hydroxychloroquine with Azithromicin, but we’ll get to that in a minute.

There is no ‘pneumonia’ nor ARDS. At least not the ARDS with established treatment protocols and procedures we’re familiar with. Ventilators are not only the wrong solution, but high pressure intubation can actually wind up causing more damage than without, not to mention complications from tracheal scarring and ulcers given the duration of intubation often required… They may still have a use in the immediate future for patients too far to bring back with this newfound knowledge, but moving forward a new treatment protocol needs to be established so we stop treating patients for the wrong disease.

The past 48 hours or so have seen a huge revelation: COVID-19 causes prolonged and progressive hypoxia (starving your body of oxygen) by binding to the heme groups in hemoglobin in your red blood cells. People are simply desaturating (losing o2 in their blood), and that’s what eventually leads to organ failures that kill them, not any form of ARDS or pneumonia. All the damage to the lungs you see in CT scans are from the release of oxidative iron from the hemes, this overwhelms the natural defenses against pulmonary oxidative stress and causes that nice, always-bilateral ground glass opacity in the lungs. Patients returning for re-hospitalization days or weeks after recovery suffering from apparent delayed post-hypoxic leukoencephalopathy strengthen the notion COVID-19 patients are suffering from hypoxia despite no signs of respiratory ‘tire out’ or fatigue.

Here’s the breakdown of the whole process, including some ELI5-level cliff notes. Much has been simplified just to keep it digestible and layman-friendly.

Your red blood cells carry oxygen from your lungs to all your organs and the rest of your body. Red blood cells can do this thanks to hemoglobin, which is a protein consisting of four “hemes”. Hemes have a special kind of iron ion, which is normally quite toxic in its free form, locked away in its center with a porphyrin acting as it’s ‘container’. In this way, the iron ion can be ‘caged’ and carried around safely by the hemoglobin, but used to bind to oxygen when it gets to your lungs.

When the red blood cell gets to the alveoli, or the little sacs in your lungs where all the gas exchange happens, that special little iron ion can flip between FE2+ and FE3+ states with electron exchange and bond to some oxygen, then it goes off on its little merry way to deliver o2 elsewhere.

Here’s where COVID-19 comes in. Its glycoproteins bond to the heme, and in doing so that special and toxic oxidative iron ion is “disassociated” (released). It’s basically let out of the cage and now freely roaming around on its own. This is bad for two reasons:

1) Without the iron ion, hemoglobin can no longer bind to oxygen. Once all the hemoglobin is impaired, the red blood cell is essentially turned into a Freightliner truck cab with no trailer and no ability to store its cargo.. it is useless and just running around with COVID-19 virus attached to its porphyrin. All these useless trucks running around not delivering oxygen is what starts to lead to desaturation, or watching the patient’s spo2 levels drop. It is INCORRECT to assume traditional ARDS and in doing so, you’re treating the WRONG DISEASE. Think of it a lot like carbon monoxide poisoning, in which CO is bound to the hemoglobin, making it unable to carry oxygen. In those cases, ventilators aren’t treating the root cause; the patient’s lungs aren’t ‘tiring out’, they’re pumping just fine. The red blood cells just can’t carry o2, end of story. Only in this case, unlike CO poisoning in which eventually the CO can break off, the affected hemoglobin is permanently stripped of its ability to carry o2 because it has lost its iron ion. The body compensates for this lack of o2 carrying capacity and deliveries by having your kidneys release hormones like erythropoietin, which tell your bone marrow factories to ramp up production on new red blood cells with freshly made and fully functioning hemoglobin. This is the reason you find elevated hemoglobin and decreased blood oxygen saturation as one of the 3 primary indicators of whether the shit is about to hit the fan for a particular patient or not.

2) That little iron ion, along with millions of its friends released from other hemes, are now floating through your blood freely. As I mentioned before, this type of iron ion is highly reactive and causes oxidative damage. It turns out that this happens to a limited extent naturally in our bodies and we have cleanup & defense mechanisms to keep the balance. The lungs, in particular, have 3 primary defenses to maintain “iron homeostasis”, 2 of which are in the alveoli, those little sacs in your lungs we talked about earlier. The first of the two are little macrophages that roam around and scavenge up any free radicals like this oxidative iron. The second is a lining on the walls (called the epithelial surface) which has a thin layer of fluid packed with high levels of antioxidant molecules.. things like abscorbic acid (AKA Vitamin C) among others. Well, this is usually good enough for naturally occurring rogue iron ions but with COVID-19 running rampant your body is now basically like a progressive state letting out all the prisoners out of the prisons… it’s just too much iron and it begins to overwhelm your lungs’ countermeasures, and thus begins the process of pulmonary oxidative stress. This leads to damage and inflammation, which leads to all that nasty stuff and damage you see in CT scans of COVID-19 patient lungs. Ever noticed how it’s always bilateral? (both lungs at the same time) Pneumonia rarely ever does that, but COVID-19 does… EVERY. SINGLE. TIME.

— — — — — — — — — — — — -

Once your body is now running out of control, with all your oxygen trucks running around without any freight, and tons of this toxic form of iron floating around in your bloodstream, other defenses kick in. While your lungs are busy with all this oxidative stress they can’t handle, and your organs are being starved of o2 without their constant stream of deliveries from red blood cell’s hemoglobin, and your liver is attempting to do its best to remove the iron and store it in its ‘iron vault’. Only its getting overwhelmed too. It’s starved for oxygen and fighting a losing battle from all your hemoglobin letting its iron free, and starts crying out “help, I’m taking damage!” by releasing an enzyme called alanine aminotransferase (ALT). BOOM, there is your second of 3 primary indicators of whether the shit is about to hit the fan for a particular patient or not.

Eventually, if the patient’s immune system doesn’t fight off the virus in time before their blood oxygen saturation drops too low, ventilator or no ventilator, organs start shutting down. No fuel, no work. The only way to even try to keep them going is max oxygen, even a hyperbaric chamber if one is available on 100% oxygen at multiple atmospheres of pressure, just to give what’s left of their functioning hemoglobin a chance to carry enough o2 to the organs and keep them alive. Yeah we don’t have nearly enough of those chambers, so some fresh red blood cells with normal hemoglobin in the form of a transfusion will have to do.

The core point being, treating patients with the iron ions stripped from their hemoglobin (rendering it abnormally nonfunctional) with ventilator intubation is futile, unless you’re just hoping the patient’s immune system will work its magic in time. The root of the illness needs to be addressed.

Best case scenario? Treatment regimen early, before symptoms progress too far. Hydroxychloroquine (more on that in a minute, I promise) with Azithromicin has shown fantastic, albeit critics keep mentioning ‘anecdotal’ to describe the mountain, promise and I’ll explain why it does so well next. But forget straight-up plasma with antibodies, that might work early but if the patient is too far gone they’ll need more. They’ll need all the blood: antibodies and red blood cells. No help in sending over a detachment of ammunition to a soldier already unconscious and bleeding out on the battlefield, you need to send that ammo along with some hemoglobin-stimulant-magic so that he can wake up and fire those shots at the enemy.

The story with Hydroxychloroquine
All that hilariously misguided and counterproductive criticism the media piled on chloroquine (purely for political reasons) as a viable treatment will now go down as the biggest Fake News blunder to rule them all. The media actively engaged their activism to fight ‘bad orange man’ at the cost of thousands of lives. Shame on them.

How does chloroquine work? Same way as it does for malaria. You see, malaria is this little parasite that enters the red blood cells and starts eating hemoglobin as its food source. The reason chloroquine works for malaria is the same reason it works for COVID-19 — while not fully understood, it is suspected to bind to DNA and interfere with the ability to work magic on hemoglobin. The same mechanism that stops malaria from getting its hands on hemoglobin and gobbling it up seems to do the same to COVID-19 (essentially little snippets of DNA in an envelope) from binding to it. On top of that, Hydroxychloroquine (an advanced descendant of regular old chloroquine) lowers the pH which can interfere with the replication of the virus. Again, while the full details are not known, the entire premise of this potentially ‘game changing’ treatment is to prevent hemoglobin from being interfered with, whether due to malaria or COVID-19.

No longer can the media and armchair pseudo-physicians sit in their little ivory towers, proclaiming “DUR so stoopid, malaria is bacteria, COVID-19 is virus, anti-bacteria drug no work on virus!”. They never got the memo that a drug doesn’t need to directly act on the pathogen to be effective. Sometimes it’s enough just to stop it from doing what it does to hemoglobin, regardless of the means it uses to do so.

Anyway, enough of the rant. What’s the end result here? First, the ventilator emergency needs to be re-examined. If you’re putting a patient on a ventilator because they’re going into a coma and need mechanical breathing to stay alive, okay we get it. Give ’em time for their immune systems to pull through. But if they’re conscious, alert, compliant — keep them on O2. Max it if you have to. If you HAVE to inevitably ventilate, do it at low pressure but max O2. Don’t tear up their lungs with max PEEP, you’re doing more harm to the patient because you’re treating the wrong disease.

Ideally, some form of treatment needs to happen to:

Inhibit viral growth and replication. Here plays CHQ+ZPAK+ZINC or other retroviral therapies being studies. Less virus, less hemoglobin losing its iron, less severity and damage.
Therapies used for anyone with abnormal hemoglobin or malfunctioning red blood cells. Blood transfusions. Whatever, I don’t know the full breadth and scope because I’m not a physician. But think along those lines, and treat the real disease. If you’re thinking about giving them plasma with antibodies, maybe if they’re already in bad shape think again and give them BLOOD with antibodies, or at least blood followed by plasma with antibodies.
Now that we know more about how this virus works and affects our bodies, a whole range of options should open up.
Don’t trust China. China is ASSHOE. (disclaimer: not talking about the people, just talking about the regime). They covered this up and have caused all kinds of death and carnage, both literal and economic. The ripples of this pandemic will be felt for decades.

https://web.archive.org/web/20200405061346/https://medium.com/@agaiziunas/covid-19-had-us-all-fooled-but-now-we-might-have-finally-found-its-secret-91182386efcb

Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites 2009 Mar 24
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660061/

We also introduced a furin cleavage site at both the S2′ cleavage site within S2 793-KPTKR-797 (S2′), as well as at the junction of S1 and S2. Introduction of a furin cleavage site at the S2′ position allowed trypsin-independent cell–cell fusion, which was strongly increased by the presence of a second furin cleavage site at the S1–S2 position. Taken together, these data suggest a novel priming mechanism for a viral fusion protein, with a critical proteolytic cleavage event on the SARS-CoV S protein at position 797 (S2′), acting in concert with the S1–S2 cleavage site to mediate membrane fusion and virus infectivity.

The coronavirus spike protein (S) mediates both receptor binding (via the S1 domain) and membrane fusion (via the S2 domain) and shows many features of conventional class I fusion proteins, including the presence of distinct heptad repeats within the fusion domain.

Some coronaviruses, notably the group 3 avian infectious bronchitis virus (IBV), are efficiently cleaved at the boundary between the S1 and S2 domains, many other coronaviruses apparently remain uncleaved. Early reports analyzing heterologously expressed SARS-CoV spike protein indicated that most of the protein was not cleaved (10, 11), but there was some possibility of limited cleavage at the S1–S2 position (11). However, S1–S2 cleavage could be enhanced by expression of furin family enzymes

2019-nCoV binds to ACE2 with much higher affinity (10-20 times higher!) than SARS. 4

Are there closely related circulating coronaviruses in bats or other animals with the novel PRRA cleavage site found in SARS-CoV-2? 8

BetaCoV/bat/Yunnan/RaTG13/2013 was more similar to the SARS‐CoV‐2 virus than to the pangolin coronavirus and the human SARS‐CoV‐2 virus  11  A unique peptide (PRRA) insertion region in the spike protein at the junction of S1 and S2 junction in the human SARS‐CoV‐2 virus (“Clade A”) induced a furin cleavage motif (RRAR), which could be a predicted polybasic cleavage site, and thus a unique feature of SARS‐CoV‐2, in comparison with the other three clades. 

SARS‐CoV‐2 is evolving at a rate of 1.24 × 10−3 substitutions per site per year. This result suggests a minor clock‐like pattern of molecular evolution, with an estimated substitution rate of 3.3452 × 10−4 substitutions per site per year and a most recent common ancestor occurring on 19 October 2019 respectively, in accordance with the root‐to‐tip regression results.

Coronaviruses are known to circulate in mammals and birds, and scientists have already suggested that nCoV-2019 originally came from bats, a proposal based on the similarity of its genetic sequence to those of other known coronaviruses. But the virus was probably transmitted to humans by another animal. 10

Structural similarity analysis of spike proteins of SARS-CoV-2 and other SARS-related coronaviruses
RaTG13 is likely to be the origin of SARS-CoV-2 because of the close similarity of the S1 domain, which is associated with the high-infectivity characteristic of SARS-CoV-2. A new amino acid insertion event of proline-arginine-arginine-alanine (PRRA) was detected between RaTG13 and SARS-CoV-2.  Furthermore, SARS-CoV-2 has a unique furin cleavage site insertion (PRRA) not found in any other CoVs in the Sarbecovirus group,  although similar motifs are also found in MERS and more divergent bat CoVs. 

Comparing WuhanHu-1 to Pan_SL-CoV_GD and RaTG13, as representative of distinct host-species branches in the evolutionary history of SARS-CoV-2, using the recombination detection tool RIP (16), we find significant recombination breakpoints before and after the ACE2 binding site, suggesting that SARS-CoV-2 carries a history of cross-species recombination between the bat and the pangolin CoVs. 


The very distinctive RaTG13 RBM suggests that this virus is unlikely to infect human cells, and that the acquisition of a complete functional RBM by a RaTG13-like CoV through a recombination event with a Pan_SL-CoV_GD-like virus enabled it to use ACE2 for human infection. 9 Thus, it is plausible that an RaTG13-like virus served as a progenitor to generate SARS-CoV-2 by gaining a complete human ACE2 binding RBM from Pan_SL-CoV_GD-like viruses through recombination.

Despite the genomic similarity between SARS-CoV and SARS-CoV-2, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows considerable difference compared to SARS-CoV, due to the presence of several point mutations. 5

Furin, a potential therapeutic target for COVID-19
Based on these three conjectures, we compared the Spike sequences from SARS-CoV-2, SARS-CoV, MERS-CoV and Bat-CoVRaTG13, and found that anextra “PRRA”insert near the  S1/S2 cleavage site. The “PRRA” insert and subsequent arginine (R) constitute a RRAR sequence that can be recognized and cleaved by furin-like proteases, which may be the reason why SARS-CoV-2 infection is stronger than SARS-CoV. What's more, we performed a homologous alignment and phylogenetic analysis of the SARS-CoV-2 sequence, and found that “PRRA”insert did not appear at any other close relatives of SARS-CoV-2, indicating that this insertwas completely novel in this genus virus. The existence of such a motif may allow Spikes to be cut into S1 and S2 by furin-like proteases before maturity, but not separated, which provides S1 with the flexibility to change the conformation to better fit the host receptor. According to Simmons G et al. studies, overexpression of furin can increase the activity of SARS-CoVSpike, but it will not cause Spike to be cleaved. 1


Multiple sequence alignment of 1000 Spike proteins. These 156 proteins were ranked according to their homology with SARS-2.The sequence corresponding to PRRA in SARS-CoV-2 in each sequence is marked in the red box.



By probing the features of the SARS-CoV-2 spike protein and the receptor with x-rays, Li and his colleagues discovered, for the first time, that just a few mutations had made a molecular “ridge” in the spike protein more compact than a similar structure in the 2002–2003 virus This and other changes helped SARS-CoV-2 attach more strongly to the receptor, infect human cells better, and spread faster.

The Leap to Humanity
The researchers also discovered that a bat coronavirus recognizes the same human receptor as SARS-CoV-2, but the bat virus attaches to the human receptor rather poorly. However, a few mutations in the spike protein may have enhanced the ability of the bat virus to attach to the human receptor, leading to the bat virus jumping to humans and evolving to become SARS-CoV-2. Previous work by Li and others showed that one particular mutation allowed the 2002–2003 virus to get into human population; in the current work, it appeared that a number of mutations might be needed for SARS-CoV-2 to jump from bats to humans.

Also, two coronaviruses have been isolated from pangolins—a type of scaly, anteater-like mammal—in China. The researchers analyzed the structures of their spike proteins and found that one of the pangolin viruses could recognize the human receptor well, implying that pangolins might have helped the bat virus jump to humans by acting as intermediate hosts. 2

Structural basis of receptor recognition by SARS-CoV-2
The overall structural similarity in hACE2 binding by SARS-CoV-2 and SARS-CoV supports a close evolutionary relationship between the two viruses. 3 SARS-CoV-2 RBDs have significantly higher hACE2-binding affinity than SARS-CoV RBD. Our study finds that compared with SARS-CoV, SARS-CoV-2 RBM contains structural changes in the hACE2-binding ridge, largely caused by a four-residue motif (residues 482-485: Gly-Val-Glu-Gly). This structural change allows the ridge to become more compact and form better contact with the N-terminal helix of hACE2

Both virus-binding hotspots have become more stabilized at the RBM/hACE2 interface through interactions with SARS-CoV-2 RBM. As our previous studies showed11,12, these hotspots on hACE2 are critical for coronavirus binding because they involve two lysine residues that need to be accommodated properly in hydrophobic environments. Neutralizing the charges of the lysines is key to the binding of coronavirus RBDs to hACE2. SARS-CoV-2 RBM has evolved strategies to stabilize the two hotspots: Gln493 and Leu455 stabilize hotspot-31, whereas Asn501 stabilizes hotspot-353. Our biochemical data confirm that SARS-CoV-2 RBD has significantly higher hACE2-binding affinity than SARS-CoV RBD and that the above structural features of SARSCoV-2 RBM contribute to SARS-CoV-2’s high hACE2-binding affinity. Thus, both structural and biochemical data reveal that SARS-CoV-2 RBD recognizes hACE2 better than SARS-CoV RBD does.


1. http://chinaxiv.org/user/download.htm?id=30223
2. https://research.umn.edu/inquiry/post/researchers-find-key-and-vulnerable-features-novel-coronavirus
3. https://www.nature.com/articles/s41586-020-2179-y_reference.pdf
4. https://theconversation.com/revealed-the-protein-spike-that-lets-the-2019-ncov-coronavirus-pierce-and-invade-human-cells-132183
5. https://www.researchgate.net/publication/340230071_Understanding_the_Role_of_Key_Point_Mutations_in_Receptor_Binding_Domain_of_SARS-CoV-2_Spike_Glycoprotein
6. https://en.wikipedia.org/wiki/Misinformation_related_to_the_2019%E2%80%9320_coronavirus_pandemic
7. https://healthfeedback.org/claimreview/contrary-to-claims-in-viral-social-media-posts-wuhan-coronavirus-was-not-lab-created-nor-was-it-patented-years-before-outbreak/?fbclid=IwAR1acvvhLKFmPbu-X7Un-esAQdwggTW8e8b9tzoAK4MnEuQ_0UOIBS1375Q
8. https://www.dhs.gov/sites/default/files/publications/2020_03_18_mql_covid-19-sars-cov-2_-_cleared_for_public_release_0.pdf
9. https://www.biorxiv.org/content/10.1101/2020.03.20.000885v2.full.pdf
10. https://www.nature.com/articles/d41586-020-00364-2
11. https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25731

Wiki: Misinformation related to the 2019–20 coronavirus pandemic
Some misinformation and disinformation claimed the virus was a bio-weapon with a patented vaccine, a population control scheme, or the result of a spy operation. Some of these misinformation and conspiracy theories may have state involvement 6

A virus, that has 30000 nucleotides, and 1.24 × 10−3 substitutions per site per year: How much time does it take to have an addition of CCT CGG CGG GCA in the genome?

Manipulation of the Coronavirus Genome Using Targeted RNA Recombination with Interspecies Chimeric Coronaviruses
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120397/

No pangolin CoV has yet been identified that is sufficiently similar to SARS-CoV-2 across its entire genome to support direct human infection. In addition, the pangolin CoV does not carry a polybasic cleavage site insertion. For a precursor virus to acquire the polybasic cleavage site and mutations in the spike protein suitable for human ACE2 receptor binding, an animal host would likely have to have a high population density – to allow natural selection to proceed efficiently – and an ACE2 gene that is similar to the human orthologue. Further characterization of CoVs in pangolins and other animals that may harbour SARS-CoV-like viruses should be a public health priority.

A specific insertion or recombination event is required to enable the emergence of SARS-CoV-2 as an epidemic pathogen.

There are also documented instances of the laboratory acquisition of SARS-CoV-1 by laboratory personnel working under BSL-2 containment. We must therefore consider the possibility of a deliberate or inadvertent release of SARS-CoV-2. Identifying the immediate non-human animal source and obtaining virus sequences from it would be the most definitive way of revealing virus origins.


http://virological.org/t/the-proximal-origin-of-sars-cov-2/398

Tackling Rumors of a Suspicious Origin of nCoV2019

I have been privately dealing with rumors and inquiries, focused on the RRAR potential furin cleavage site, that nCoV2019 may have a suspicious origin as an engineered, laboratory-generated virus either accidentally or deliberately released in the area of the Wuhan seafood and animal market. The publication of the highly similar RaTG13 sequence about a week ago has fueled this type of speculation.

As I have told people privately, I see no evidence at all to support such a claim. In sharp contrast, I have studied the question in detail, using RaTG13 and Wuhan sequence at the S1/S2 boundary, and find convincing proof of exactly opposite conclusion – that RaTG13 could NOT be a proximal source of the Wuhan virus.

At first glance of an alignment of the S protein sequence of both, it is natural that the issue of an engineered insertion should be considered. On either side of the new furin site, the amino acid sequence is identical in both from aa614 to aa1133 – an apparent insert of PRRA is the only difference in an otherwise 100% conserved 519 amino acid region.

But that is at first glance.

One has to consider that the PRRA is an unusual sequence to introduce to generate a furin site – others even among coronaviruses like MHV A59 are so much better. Also that the underlying code CCTCGGCGGGCA introduces an unnecessarily G and C rich region where none otherwise exists. Not likely scenarios for something a gene jockey would do.

My comment:
This is a poor argument. The insertion is achieving tremendous harm - it had not to be perfect. It had only to be good enough. And if it were engineered, the designers would certainly not use a sequence that could easily be detected as designed insertion, but spend efforts to hide it. 

Then one looks at the actual RNA alignment. The “insert” is actually not in frame, but CTCCTCGGCGGG, or -2 out of frame. Again, who does that?

But the PROOF lies in looking at the 288 alignable nucleotides on either side of the “insert”. While they cover identical protein sequence, the RNA is not at all identical, but 6.6% different – 19 mutations out of 288. All 19 are mutations in the wobble base of their respective codons. There are so many that the frame can be inferred from the 2/1 pattern even without knowing the beginning or the end, or indeed that the encoded protein sequence is identical – those are self-evident by looking at the RNA itself.

We know from influenza H1N1, for which we have serial isolates from 1918 to the present, that wobble base mutagenesis occurs at a rate of 0.95% per decade. This permits an estimation of the TMRCA of the two sequences nCoV2019 and RaTG13 of 69.5 years ago – roughly 1950 +/- 10 years or so.

RaTG13, or anything nearly identical to it at the RNA level, simply could not be a proximal source of nCoV2019. It just LOOKS like it might be…at first glance.

Given that furin cleavage signals are present in other coronaviruses at exactly that point in the S1/S2 boundary region, it only LOOKS unusual, especially against the backdrop of SARS. The preponderance of evidence, coupled with Ockham’s razor (that the simplest explanation is preferred) dictates that the PRRA sequence has been conserved in nCoV2019 from a long-ago ancestor virus. It is not of suspicious origin. The closest bat virus sequence is really not close at all.

My comment:
Wow !! It seems to me, that the conclusion should be PRECISELY the opposite !!. If the nCoV2019 has been conserved, then why has it been discovered only now? And why has it not infected humans before? 


http://virological.org/t/tackling-rumors-of-a-suspicious-origin-of-ncov2019/384

Did COVID-19 Virus Evolve by Natural Selection?

https://evolutionnews.org/2020/03/did-covid-19-virus-evolve-by-natural-selection/

Does the conclusion of this article fit? It goes like this:

Design and Evolution
Myers, like the Nature Medicine scientists, uses the scientific inference to intelligent design to search for (and discount) human intelligent agency. Design science is at the forefront of research on the emergence of coronavirus. Based on the available evidence and using the inference to design as a scientific hypothesis, intelligent design of the COVID-19 virus seems unlikely.

But there is another lesson about design and evolution to be learned from scientific research on this virus. Natural selection, if understood as undirected variation and differential reproductive success, is a destructive process. Natural selection destroys biological functional complexity — it produces diseases, cancer, and pandemics. It weakens and kills. Natural selection does to living organisms what rust does to a machine. Natural selection corrodes and destroys life, and plays no role in creating it.

My comment:
if the additional sequence that turns COVID 19 so lethal were a product of natural selection, as the PZ Myers claims, and Egnor concurs, the follow-up conclusion does not logically follow.

COVID 19, if it were the product of natural selection, did NOT destroy biological functional complexity. Quite the contrary is the case: scientists have not seen anything like this in previous strains. But, it was not just a single anomaly. It adds: “Before the emergence of the 2019-nCoV, this important feature was not observed in other coronaviruses.

Strikingly, the 2019-nCoV sequence contains 12 additional nucleotides upstream of the single cleavage site.”

The paper suggests that this part of the DNA chain has been tampered with for

“gain-of-function

to the 2019-nCoV for efficient spreading in the human population compared to other coronaviruses".

So the additional nucleotides did NOT deteriorate the genome but provide a GAIN OF FUNCTION, which is helping the Virus to be enormously successful.

While people are dying, the Virus is well and alive and multiplicating.

Natural selection , if it was the cause of the sequence, is in this case, a TREMENDOUS SUCCESS for the viruses...

The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade.
https://www.ncbi.nlm.nih.gov/pubmed/32057769

Strikingly, the 2019-nCoV S-protein sequence contains 12 additional nucleotides upstream of the single Arg↓ cleavage site 1 (Fig. 1, Fig. 2) leading to a predictively solvent-exposed PRRAR↓SV sequence, which corresponds to a canonical furin-like cleavage site (Braun and Sauter, 2019; Izaguirre, 2019; Seidah and Prat, 2012). This furin-like cleavage site, is supposed to be cleaved during virus egress (Mille and Whittaker, 2014) for S-protein “priming” and may provide a gain-of-function to the 2019-nCoV for efficient spreading in the human population compared to other lineage b betacoronaviruses.

A virus, that has 30000 nucleotides, and 1.24 × 10−3 substitutions per site per year: How much time does it take to have an addition of CCT CGG CGG GCA in the genome? if that addition could be demonstrated to be plausibly the result of recombination by natural selection, then it would as well be a great argument for advocates of darwinian evolution.

Evidence of recombination in coronaviruses implicating pangolin origins of nCoV2019
https://www.biorxiv.org/content/10.1101/2020.02.07.939207v1.full.pdf

Amino acid alignment between pangolin coronavirus and nCoV-2019 at the S1-NTD subdomain results in low sequence similarity. However, increased similarity is observed from the RBD through the S2 domain. This suggests a possible recombination event between a bat coronavirus and the pangolin coronavirus at the S1-NTD and RBD junction. While there is high conservation at the amino-acid level between the pangolin coronavirus and nCoV-2019, this is not reflected in the nucleotide identity, suggesting that the proposed recombination event occurred in the more distant past, allowing subsequent time for genetic drift. One such mutation could be the insertion of the amino acid residues PRRA near the S1/S2 junction which induces a furin cleavage motif.

Obama Warned The U.S. To Prepare For A Pandemic Back In 2014

....and in order for us to deal with that effectively we have to put in place an infrastructure not just here at home but globally that allows us to see it quickly isolate it quickly respond to it so that

if and when a new strain of flu-like the Spanish flu crops up five years from now 

or a decade from now we've made the investment and we're further along to be able to catch it the funding we're asking for is needed to keep strengthening our capacity here at home so we can respond to any future Ebola cases it's needed to help us partner with other countries to prevent and deal with future outbreaks and threats before they become epidemics we were lucky with h1n1 that it did not prove to be more deadly we can't say we're lucky with Ebola because obviously it's having a devastating effect in effect in West Africa but it is not airborne in its transmission 

there are may and likely will come a time in which we have both an airborne disease that is deadly

it is a smart investment for us to make it's not just insurance it is knowing that down the road 


we're going to continue to have problems like this particularly in a globalized world where you move from one side of the world to the other in a day so this is important now but it's also important for our future and our children's future and our grandchildren's future

I cannot think of a better example of an area where we should all agree than passing this emergency funding to fight Ebola and to set up some of the public health infrastructures that we need to deal with potential outbreaks in the future 

do you know a lot of people think that goes away in April with the heat as the heat comes in typically that will go away at April this moment we think we have it very much in hand dr. Fauci he said earlier this week that the lag in testing was in fact a failing do you take responsibility for that yeah no I don't take responsibility at all said that you don't take responsibility but you did disband the white house pandemic office and the officials that were working in that office left this administration abruptly so what responsibilities do you take to that and the officials that worked in that office said that you that the White House lost valuable time because that office wasn't disbanded what do you make of that well I just think it's a nasty question because what we've done is and Tony had said numerous times that we saved thousands of lives because of the quick closing and when you say me I didn't do it we have a group of people I could I could ask perhaps it may have been stray ship but I could perhaps ask Tony about that because I don't know anything about some of the people we cut they haven't been used for many many years and if they if we have a need and we can get them very quickly and rather than spending the money and I'm a business person I don't like having thousands of people around when you don't need


https://www.youtube.com/watch?v=pBVAnaHxHbM

A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence
https://www.nature.com/articles/nm.3985?fbclid=IwAR1zYsHDEX61zdJRDLGdQsL7j602-QeT3zCoK4vuctLjhliGlV45Z8dOaD8

Mutations, Recombination and Insertion in the Evolution of 2019-nCoV
https://www.biorxiv.org/content/10.1101/2020.02.29.971101v1.abstract

2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site.

Evidence that in the last few years, laboratories have experimented to find gain-of-function motifs like the amino acid sequence PRRA in Covid 19, used by furin proteases as cleavage sites to activate infection,  causing our current pandemic outbreak !! 

Mutations, Recombination and Insertion in the Evolution of 2019-nCoV 2
March 02, 2020

2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site.  

Wikipedia: 4
The novel coronavirus of 2019/20 are activated by TMPRSS2

Functional analysis of potential cleavage sites in the MERS-coronavirus spike protein 3
09 November 2018, Markus Hoffmann,  Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Kellnerweg 4, 37077, Göttingen, Germany

Pre-cleavage at the S1/S2 motif (RSVR) was important although not essential for subsequent MERS-S activation by TMPRSS2, and indirect evidence was obtained that this motif is processed by a protease depending on an intact RXXR motif, most likely furin.

Furin is a recombinant, ubiquitous subtilisin-like proprotein convertase with a minimal cleavage site of Arg-X-X-Arg˅. However, the enzyme prefers the site Arg-X-Lys/Arg-Arg˅. 6

Discussion
MERS-CoV infection is associated with a case-fatality rate of 36% and the virus has pandemic potential
Therefore, development of antiviral strategies is an important task. The activation of the viral spike protein (S) by host cell proteases is essential for viral infectivity and the responsible enzymes are potential therapeutic targets. The cellular proteases furin, cathepsin L and TMPRSS2 can activate MERS-S and may cleave the S protein at two distinct sites, termed S1/S2 and S2′. Moreover, a potential cathepsin L cleavage site in MERS-S has been reported.

Our data support the concept that pre-cleavage of MERS-S at the S1/S2 site by furin promotes subsequent S protein activation by TMPRSS2. 

My comment:
This could DIRECT AND HARD evidence that the PRRAR↓SV sequence, which corresponds to a canonical furin-like cleavage site which is supposed to be cleaved during virus egress for S-protein “priming” and provides a gain-of-function to the 2019-nCoV for efficient spreading in the human population compared to other lineage b betacoronaviruses 1 WAS AN INTRODUCTION NOT BY NATURAL RECOMBINATION, an evolutionary process in nature,  BUT GENETIC LABORATORY ENGINEERING.

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor 5
March 05, 2020 Markus Hoffmann,  Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Kellnerweg 4, 37077, Göttingen, Germany

Addition & conclusion: 
After an e-mail exchange with Dr.Hoffmann, I am concluding that COVID 19 is most probably a variation from a recombination event, that occurs naturally in nature. 



1. https://www.ncbi.nlm.nih.gov/pubmed/32057769
2. https://www.biorxiv.org/content/10.1101/2020.02.29.971101v1.abstract
3. https://www.nature.com/articles/s41598-018-34859-w
4. https://en.wikipedia.org/wiki/TMPRSS2
5. https://www.cell.com/cell/fulltext/S0092-8674(20)30229-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420302294%3Fshowall%3Dtrue#%20
6. https://international.neb.com/products/p8077-furin#Product%20Information